DESCRIPTION (adopted from the application): Sporozoites exhibit infectivity for both mosquito salivary glands and vertebrate host tissues, and therefore they are a critical stage in the development of the parasite that can be exploited in efforts to control or eradicate malaria. New control measures involving vaccines, drug therapy and novel mosquito control methods are needed, and efforts toward this end have been expedited with the recent genomic and proteomic advances in the field of malaria research. This application describes an in silico, or data "mining" approach to selecting novel Plasmodium falciparum sporozoite genes that are translationally expressed in sporozoites, that contain a signal peptide sequence, and that are predicted, via sequence analysis, to be on the surface of or secreted by sporozoites. The hypothesis of this research is that the selected genes expressed by the sporozoite play a role in invading the vector and/or vertebrate host tissues. The specific aims of this research are the following: (1) to determine the cellular location of the proteins encoded by the three P. falciparum sporozoite genes that are selected following mining of PlasmoDB, and likewise to characterize Pf4, a homolog of Pg4 that is a surface molecule on P. gallinaceum sporozoites;(2) to perform a functional analysis of the four selected sporozoite genes using gene knock-out technology;and (3) to compare the proteome profiles of the mutant P. falciparum sporozoites with the wild-type strains to determine the impact of the selected genes on other gene products and pathways in the sporozoite. This research should elucidate the function of the four selected genes and help to identify their roles in sporozoite biology. In addition, a beginning will be made to assess the impact of the selected genes on other genes and processes or pathways in the sporozoite using state-of-the-art proteomic technologies. Ultimately, potential vaccine candidates and/or molecules that could be used to genetically manipulate the mosquito vector to prevent disease transmission could be discovered and eventually exploited to provide new additions to the arsenal of weapon available to better control malaria.